This proposal is concerned with certain design variables affecting bone remodeling following primary cementless total hip arthroplasty. The use of cementless techniques in total hip arthroplasty heightens concern with stress-induced bone remodeling, fixation, and long term biocompatibility. Proximal cortical resorption of varying severity has been reported with a variety of cementless femoral stems, made from CoCr or from Ti6Al4V. Cortical resorption can lead to failure of the host bone, failure of the prosthetic device, and presents enormous problems for further reconstruction. The purpose of this proposal is to gain a better understanding of the relationship between stress-induced bony changes in the proximal femur following cementless total hip arthroplasty (THA) and implant design. We propose to investigate this relationship by studying bone remodeling as a function of cross-sectional stiffness related to stem modulus and stem geometry. Two hypotheses will be tested. (1) The elastic modulus and geometry of the femoral stem can be modulated to minimize long-term femoral remodeling changes. (2) The relationship between prosthetic-induced changes in the femur's mechanical environment and adaptive changes in cortical morphology is non-linear. Specifically, we plan to evaluate the effect of large variations in stem (i) elastic modulus and (ii) geometry (in this study, the location of the implant's centroids and bending axes relative to those of the femur) on changes in bone morphology in a canine model, while accounting for individual variation in the position of the stem within the femoral canal. These data will be used to determine if the relationship between the prosthesis-induced changes in femoral stress/strain and the changes in bone morphology is linear or non-linear. Thus, two key clinical questions are (i) how does bone remodeling vary over the range of relative stem stiffness of potential clinical feasibility and (ii) does stem geometry influence proximal bone loss following cementless THA? To address these issues, a canine primary THA model will be used in which stem stiffness will be varied over a 10-fold range. In a separate experiment, stem shape will be varied. The experimental endpoints will be the structural responses to the treatments (e.g., change in cortical area, thickness and porosity and medullary bone density). The data will be analyzed to test for the effects of the design variables on the remodeling response and to determine mechanistically how the prosthesis-induced changes in the mechanical environment of the femur correspond to the bony adaptive response. The goal of these experiments is to derive principles which will have clinical implications.